Nevirapine in an animal model of pre-diabetes: study of drug pharmacokinetic and its effects on fasting glycemia and insulin resistance

Dissertação para obtenção do Grau de Mestre em BiotecnologiaThe increased incidence of type II diabetes has emerged as a major concern in controlled human immunodeficiency virus (HIV)infection. There is a general lack of data to support the best combined antiretroviral therapy (cART) option to treat HIV-patients with pre-diabetes and nevirapine has been described has a glucose-friendly antiretroviral. On the other hand, it is known that diabetes could influence the pharmacokinetics of several drugs. This aspect is particularly relevant for drugs with narrow therapeutic window, which is the case of nevirapine. To understand if nevirapine is a good choice for pre-diabetic HIV-patients, the effect of insulin resistance in NVP pharmacokinetics as well as the effect of nevirapine on insulin resistance, fasting glycemia and mean arterial pressure was evaluated. Moreover, nevirapine effect on thiols content, an endogenous antioxidant defence system, was also evaluated. To achieve the main goal four groups of female Wistar rat were used: a control group, a control group treated with nevirapine, an insulin resistant group and an insulin resistant group treated with nevirapine. An influence of a pre-diabetic status on nevirapine pharmacokinetic was found. Nevirapine and its phase I metabolites presented changes in disposition and the metabolite profile pattern was changed. Moreover, nevirapine, in a pre-diabetic perspective, is associated with a beneficial effect on fasting glycemia, while it has no effect on sensitivity to insulin or in arterial pressure. Furthermore, nevirapine is associated with a lower degradation of total glutathione. Nevirapine might be a good option for HIV-infected patients at higher risk of develop diabetes or in pre-diabetic condition. Moreover, while further studies are necessary to consolidate this issue, nevirapine might be less toxic in pre-diabetes. Although, the decreased bioavailability of nevirapine in pre-diabetes requires special attention, as an adjustment of nevirapine dose might be required in this subpopulation.Portuguese Foundation for Science and Technology - PTDC/QUI-QUI/113910/2009, PTDC/SAU-ORG/111417/200

Estudo químico de folhas de Pouteria ramiflora (Mart.) Radlk. (Sapotaceae) : biomonitoramento por inibição da alfa-amilase

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, 2015.Pouteria ramiflora (Mart.) Radlk., espécie comumente encontrada no Cerrado é popularmente conhecida como, “curriola” (“curiola”), “brasa-viva”, “figo-do-cerrado” entre outros. Essa planta produz frutos comestíveis e é usada na medicina popular contra hiperlipidemias e para tratar vermes, disenteria, dor e inflamação. Extratos dessa espécie apresentam atividades alelopática, anti-inflamatória, antinociceptiva, antimicrobiana, antioxidante, citotóxica, mutagênica, neuroprotetora, sendo útil no controle glicêmico e de peso. Pouteria ramiflora apresenta ainda inibição das enzimas α-amilase e α-glicosidase motivo pelo qual foi escolhida para ser estudada visando a descoberta de novos inibidores da α-amilase. A inibição dessa enzima está relacionada ao controle glicêmico em pacientes com diabetes mellitus tipo 2, uma desordem metabólica que implica em várias complicações secundárias e atinge pessoas no mundo todo. Neste trabalho foi realizado o estudo químico e o biomonitoramento da atividade inibitória da enzima α-amilase por extratos de folhas de Pouteria ramiflora. A α-amilase foi exposta aos extratos brutos, aquoso, hexânico e etanólico e a atividade da enzima foi avaliada na presença e na ausência do possível inibidor pelo método colorimétrico descrito por Bernfeld (1955), com modificações. O extrato mais ativo foi definido com a obtenção do valor de CI50 em comparação ao padrão acarbose. Esse extrato foi fracionado com o objetivo de isolar o composto ativo. Os compostos foram isolados e identificados por técnicas cromatográficas e espectrométricas como CCD, CC, CLAE-DAD, IV, CG-EM e RMN de 1H e 13C e identificados. O extrato aquoso (CI50 = 9,51 μg/mL) e a fração aquosa (CI50 = 9,71 μg/mL) desse extrato foram os mais ativos contra a enzima avaliada com valores de IC50 próximos ao padrão acaborse (CI50 = 4,2 μg/mL). Os triterpenos epifriedelanol, friedelina e taraxerol foram identificados e/ou isolados a partir do extrato hexânico e o flavonoide miricitrina, marcador do gênero, foi isolado e identificado a partir do extrato aquoso de P. ramiflora. Até onde vai o nosso conhecimento, este é o primeiro relato da identificação de epi-friedelanol, friedelina, taraxerol e do isolamento miricitrina em P. ramiflora. A presença desses compostos pode justificar, pelo menos em parte, a atividade observada nos extratos desta planta.Pouteria ramiflora (Mart.) Radlk., a species commonly found in Cerrado and populary known as curriola (curiola), brasa-viva, figo-do-cerrado among others. This plant produces edible fruits and is used in folk medicine as hyperlipaedemic and to treat worms, dysentery, pain and inflammation. Extracts of this species exhibit allelopathic, antiinflammatory, antinociceptive, antimicrobial, antioxidant, cytotoxic, mutagenic, neuroprotective activities and also is useful in glycemic and weight control. Because Pouteria ramiflora extracts present α-amylase and α-glucosidase inhibition, this species was chosen in this study toward the potential discovery of new α-amylase inhibitors. Inhibition of this enzyme is related to glycemic control in patients with diabetes mellitus type 2, a metabolic disorder that involves multiple secondary complications and affects people worldwide. In this work we performed the chemical and biomonitoring studies of the in vitro inhibition activity of extracts from Pouteria ramiflora against α-amylase enzyme. The aqueous, hexane and ethanol crude extracts were evaluated against α-amilase; and the enzyme activity was tested in the presence and absence of possible inhibitors by the colorimetric method described by Bernfeld (1955) with modifications. The IC50 was obtained and the most active extract was defined and compared to acarbose standard. This extract was fractionated with the purpose of isolating the active compound. The compounds were isolated and identified for chromatographic and spectrometric techniques such as TLC, CC, HPLC-DAD, IR, GC-MS and 1H NMR and 13C NMR and identified. Aqueous extracts ((IC50 = 9,51 μg/mL) and its aqueous fraction (IC50 = 9,51 μg/mL) were the most active against the α-amilase with the IC50 value similar to the standard acarbose (IC50 = 4,2 μg/mL). The triterpenes epi-friedelanol, friedelin and taraxerol were identified from the hexane extract and the myricitrin flavonoid, chemical marker of the genus Pouteria, was isolated and identified from the P. ramiflora aqueous extract. As far as know, this is the first report of the identification of epi-friedelanol, friedelin, taraxerol and the isolation of myricitrin from P. ramiflora. The presence of these compounds may help to clarify at least in part the reported biological activity for this species

Efeitos do fogo controlado na composição e estrutura de comunidades de pequenos mamíferos não-voadores (Ordens Didelphimorphia e Rodentia) no cerrado brasileiro

Tese de mestrado em Biologia da Conservação, Universidade de Lisboa, Faculdade de Ciências, 2020Um dos principais focos da ecologia é a determinação dos padrões de distribuição e abundância das espécies nos ecossistemas e dos mecanismos que os determinam. O conhecimento destes padrões e determinantes permite entender, de uma forma mais abrangente, quais os efeitos das alterações ambientais, como a perda de habitat, na taxa de extinção das espécies. A perda de biodiversidade global tem atingido taxas exponenciais, devido às extinções em massa que se têm registado nas últimas décadas, muitas vezes associadas a alterações climáticas e a perturbações antropogénicas, que determinam, por exemplo, a degradação e transformação de habitat. Em contrapartida, as perturbações naturais são fenómenos recorrentes nos ecossistemas que ainda não compreendemos completamente e, por isso, têm sido realizados muitos estudos para entender estes processos ecológicos e prever quais as respostas que a fauna e flora adotam face a essas perturbações, como por exemplo, o fogo natural. O fogo é um agente de perturbação direta dos ecossistemas terrestres, que provoca a destruição da vegetação e induz alterações na estrutura e composição das comunidades de flora e fauna residentes. Em certos ecossistemas, como o Cerrado (Brasil), o fogo é um fator determinante para a manutenção do equilíbrio do próprio ecossistema, uma vez que tem um papel nuclear na dinâmica populacional das comunidades de flora e fauna residentes. No entanto, os resultados de estudos previamente realizados, no que toca ao impacto dos incêndios do Cerrado nos pequenos mamíferos, mostram uma elevada variação no tipo e escala do efeito do fogo nas comunidades naturais. Enquanto alguns estudos comprovam que as comunidades de pequenos mamíferos são favorecidas por esta perturbação, outros indicam o contrário. Desta forma, os estudos já realizados são insuficientes para avaliar, de uma forma clara, os efeitos do fogo nas comunidades de pequenos mamíferos, no Cerrado. Assim, para colmatar esta lacuna de informação e contribuir para o debate atual sobre o efeito do fogo nas comunidades animais, este estudo tem como objetivo averiguar qual o efeito do fogo controlado na composição e estrutura dessas comunidades, em duas fisionomias diferentes de Cerrado – campo sujo e campo cerrado – incluídas na Estação Ecológica de Santa Bárbara, estado de São Paulo (Brasil). Em ambas as fisionomias, e antes e depois dos eventos de fogo controlado, estimámos a abundância relativa, riqueza específica e diversidade das espécies de roedores e marsupiais presentes, bem como aferimos quais os fatores ambientais e paisagísticos que determinam essas métricas, bem como a presença das espécies. As respostas demonstram que algumas espécies de roedores, como Oligoryzomys mattogrossae, Akodon montensis, Calomys tener e Cerradomys scotti são favorecidas pela ocorrência do fogo, por selecionarem habitats com uma cobertura vegetal menos densa, e porque há um atraso na resposta numérica dos predadores (i.e. em termos populacionais, os roedores respondem mais rapidamente que os predadores a eventos de fogo). Contrariamente, as espécies de marsupiais apresentaram seletividade por estádios mais avançados na sucessão, onde o estrato arbóreo está presente. Tanto a riqueza específica como a diversidade foram afetadas positivamente pelo fogo, possivelmente pelo facto de os taxa de pequenos mamíferos presentes serem mais resilientes a esta perturbação que os seus predadores. Por outro lado, as variações climáticas (i.e. temperatura e evapotranspiração), a paisagem (i.e. a cobertura de diferentes fisionomias) e a ocorrência do fogo foram os fatores mais determinantes dos padrões de riqueza específica, diversidade e abundância das espécies que compõem as comunidades de roedores e marsupiais do Cerrado. Desta forma, o uso de fogo prescrito em unidades de conservação no Cerrado, pode ser uma ferramenta para garantir a heterogeneidade de habitat, e consequentemente, manter a dinâmica das comunidades de pequenos mamíferos e, assim, assegurar a manutenção da biodiversidade.One of the main focuses of ecology is the assessment of species distribution and abundance patterns in the different ecosystems, and the drivers shaping it. The knowledge of these patterns and drivers allow us to understand, in a broader way, the effects of environmental changes, such as habitat loss, on the species' extinction rate. The loss of global biodiversity has reached exponential rates, due to the mass extinctions that have been registered in the last decades, which are often associated with climate change and anthropogenic disturbances that lead to, for example, habitat degradation and transformation. On the other hand, natural disturbances are recurrent phenomena in ecosystems which we still do not fully comprehend and, therefore, many studies have been carried out to understand the associated ecological processes and predict the responses adopted by fauna and flora to these disturbances, such as natural fire. Fire is an agent of direct disturbance to terrestrial ecosystems that causes the destruction of vegetation and changes the structure and composition of the resident flora and fauna communities. In certain ecosystems, such as the Cerrado (Brazil), fire is a determinant factor for maintaining the balance and integrity of the ecosystem, since it has a pivotal role in determining the population dynamics of the flora and fauna communities. However, the results of studies previously carried out in this Biome, targeting the impact of Cerrado fires on small mammals, showed a high variability in the type and scale of the fire’s effect in natural communities. While some studies showed that communities of small mammals are favoured by this disturbance, others prove otherwise. Thus, the studies already carried out and published are insufficient to assess the effects of fires on small mammal communities in the Cerrado Biome. Therefore, to fill this information gap and to contribute to the current debate on fire effects on wildlife, this study aims to investigate the effect of prescribed fire on the composition and structure of small mammals communities, inhabiting two different physiognomies of the Cerrado – “campo sujo” and “campo cerrado” – currently occurring in the Santa Bárbara Ecological Station, state of São Paulo (Brazil). In both physiognomies, before and after controlled fire events, we estimated the relative abundance, specific richness and diversity of rodents and marsupial mammals, as well as assessed which environmental and landscape drivers influence those metrics and the presence of species. Results show that some rodent species, such as Oligoryzomys mattogrossae, Akodon montensis, Calomys tener and Cerradomys scotti, are favoured by the occurrence of fire events, as they select habitats with less dense vegetation cover, and because there is a delay in predators numerical response (i.e. rodents population increase faster after fires than predator). In contrast, marsupial species showed a preference for more advanced successional stages, where the arboreal strata are more developed. Both specific richness and diversity were positively affected by fire, possibly due to the fact rodents and marsupials are more resilient to this disturbance than their predators. On the other hand, climatic variations (i.e temperature and evapotranspiration), landscape (i.e the cover of different physiognomies) and the presence of fire were the most influential factors shaping species richness and diversity, and the abundance of Cerrado’s rodent and marsupial species. Thus, the use of prescribed fire in conservation units in the Cerrado, can be a tool to guarantee the heterogeneity of habitat, and consequently, maintain small mammal’s communities dynamics, and thus ensure the maintenance of this Biome biodiversity

Profile of information professionals: an information science perspective based on the RIM framework

The objective of this paper is to present the preliminary results of a content analysis of the Records and Information Management: Core Competencies framework (RIM) in order to understand which Knowledges and Skills are the most mentioned. It was found that the RIM emphasizes a set of Knowledges and Skills of utmost importance for the practice of the information profession and that these can be complementary or equivalent, varying according to the qualification required of the professional. With this analysis it is expected to contribute to a better understanding of the core Knowledges and Skills of Information Professionals from an Information Science perspective.info:eu-repo/semantics/draf

Evaluation of Lower Limb Arteriovenous Diameters in Indoor Soccer Athletes: Arterial Doppler Ultrasound Study

The purpose of this study was to analyze the arterial and venous diameters of lower limbs in indoor soccer athletes and non-athletes using Doppler ultrasound to identify the differences in the variation of arterial and venous diameters between groups. Additionally, we intended to verify the differences of arterial and venous diameters between the skilled member (right member) and the not skilled member in each group. 74 male volunteers, aged between 19 and 30 years old, were divided in a group of athletes (n = 37, 24 ± 2.7 years, soccer players from national championship), and a group of non-athletes (n = 37, 26 ± 2.83 years). Vascular lower limb was assessed using Doppler ultrasound (Philips HD7 echograph with linear transducer 7–12 MHz). The athletes showed higher diameters of right common femoral artery (p = 0.009; moderate), left common femoral artery (p = 0.005; moderate), right deep femoral artery (p = 0.013; moderate), right popliteal artery (p = 0.003; moderate), and left popliteal artery (p = 0.017; small) than non-athletes. Veins’ diameters were also higher in athletes, specifically the right deep femoral vein (p ≤ 0.001; large), left deep femoral vein (p ≤ 0.001; large), right popliteal vein (p ≤ 0.001; large), and left popliteal vein (p ≤ 0.001; large). Differences were found between the skilled and non-skilled leg in athletes in the popliteal vein (7.68 ± 1.44 mm vs. 7.22 ± 1.09 mm, respectively, p < 0.003). It seems that futsal athletes have superior mean diameters of lower limbs arteries and veins of the deep venous system to non-athletes. Moreover, the veins presented greater dilation, namely of the leg of the skilled lower limb.info:eu-repo/semantics/publishedVersio

Leptospirosis: an update - parte 2 of 2: pathogenesis, clinical aspects, diagnosis and treatment / Leptospirose: uma actualização - parte 2 de 2: patogénese, aspectos clínicos, diagnóstico e tratamento

Leptospirosis belongs to the category of neglected infectious diseases and, due to its great epidemic potential, its local distribution in tropical regions is of extreme importance. It is a worldwide public health problem, known for the emergence and reappearance of the disease, lack of sanitary conditions and its abandonment. Human infections usually occur after skin contact with soil and/or water that has been contaminated by the urine of chronically infected mammals. The clinical manifestations of the disease range from mild fever, chills and flu-like symptoms to acute forms of the disease. Based on these brief considerations, this article - part 2 of 2 - aims to discuss the biological, ecoepidemiological, prophylactic and control aspects of leptospirosis in Brazil

Leptospirosis: An Update - Part 1 Of 2: Etiology, Ecology, Epidemiology, Prophylaxis And Contro / Leptospirose: Uma actualização - Parte 1 De 2: Etiologia, Ecologia, Epidemiologia, Profilaxia e Controlo

Leptospirosis belongs to the category of neglected infectious diseases and, due to its great epidemic potential, its local distribution in tropical regions is of extreme importance. It is a worldwide public health problem, known for the emergence and reappearance of the disease, lack of sanitary conditions and abandonment of the disease. Human infections usually occur after skin contact with soil and/or water contaminated by the urine of chronically infected mammals. The clinical manifestations of the disease range from mild fever, chills and flu-like symptoms to acute forms of the disease. Based on these brief considerations, this article - part 1 of 2 - aims to discuss the biological, ecoepidemiological, prophylactic and control aspects of leptospirosis in Brazil

Natriuretic Peptide System Activation in Acute Heart Failure Patients with Diabetes

Background. Elevated B-type natriuretic peptide (BNP) is a hallmark in heart failure (HF). Diabetic patients with chronic HF seem to have higher BNP than nondiabetics. We studied, in acute HF, if BNP levels are different between diabetics and nondiabetics. Methods. From a prospectively recruited population of acute HF patients, we selected a convenience sample. In pair-matched analysis, each diabetic patient was matched with a nondiabetic of the same age (±1 year), gender, and according to left ventricular systolic dysfunction. Diabetics and nondiabetics were compared. Cox-regression analysis was used to analyse the prognostic impact of diabetes. Results. We studied 328 patients, mean age: 78 years, 44.5% male. Diabetics were more often hypertensive and had ischemic HF; they had higher body mass index, lower haemoglobin, and worse renal function. Diabetics were more often discharged on ACE inhibitors/ARB, antiplatelet therapy, and statins. Neither admission nor discharge BNP values differed between diabetics and pair-matched nondiabetics. One-year mortality was also nondifferent between pairs of diabetics and nondiabetics: 44 (26.8%) and 46 (28.0%), respectively. HR for 1-year mortality in diabetics was 1.00 (95% CI: 0.82–1.24) compared with nondiabetics. Conclusions. HF patients with diabetes have similar neurohumoral activation when compared with nondiabetics. One-year mortality is also nondifferent after matching for age, gender, and systolic function

Towards a multi-marker prognostic strategy in acute heart failure: a role for GDF-15

AIMS: Growth differentiation factor (GDF)-15 mirrors inflammation and oxidative stress in cardiovascular diseases. Brain natriuretic peptide (BNP) is associated with cardiomyocyte stretch in heart failure (HF). The objective of this study was to evaluate the prognostic impact of plasma GDF-15 and BNP in acute HF. METHODS AND RESULTS: We studied a subgroup of patients prospectively recruited in an acute HF registry (follow-up: 2 years; endpoint: all-cause mortality). Cox regression multivariate models were built to study the association of GDF-15 and mortality. Further cross-classification according to discharge GDF-15 (mean) and BNP (mean) and association with mortality was studied. We studied 158 patients: seventy-nine were male, mean age was 75 years, 55.1% had left ventricular ejection fraction < 40%, mean discharge BNP was 1000 pg/mL, and mean GDF-15 was 3013 ng/mL. Higher BNP and GDF-15 predicted 2-year mortality. Patients with GDF-15 ≥ 3000 ng/mL had a multivariate adjusted 2-year death risk of 1.86 (1.08-3.18). Patients discharged with both BNP and GDF-15 above the mean had an adjusted hazard ratio of 4.33 (2.07-9.06) when compared with those with both <mean. CONCLUSIONS: Higher GDF-15 associated with worse prognosis in acute HF independently of BNP. When both biomarkers GDF-15 and BNP were elevated at discharge, the 2-year mortality risk increased over four-fold. Biomarkers related to different pathophysiological pathways can provide incremental prognostic information in acute HF.info:eu-repo/semantics/publishedVersio

Construindo as camadas do saber - kit didático de litosfera no 6° ano Ensino Fundamental da Escola Estadual Padre João Tomes - Três Lagoas/MS

Nosso relato refere-se à pesquisa realizada sobre aspectos gerais da sala de aula, bibliografias sobre o uso e montagem de kit didático e filmes relativos ao ensino de geografia; concomitante, desenvolveu-se o planejamento de uma sequência didática que buscou somar as dificuldades encontradas em sala de aula e a utilização de ferramentas didáticas e pedagógicas que potencializassem a cognição do aluno e efetivassem o processo de ensino - aprendizagem. O publico alvo foram os alunos do 6° ano da Escola Estadual Padre João Tomes, localizada no município de Três Lagoas, o conteúdo seguiu o Referencial Curricular do Mato Grosso do Sul (2012), que no 2° bimestre do referido ano, propõe o conteúdo Litosfera, que seja trabalhado discutindo os seguintes tópicos: (Formação do Planeta Terra, A estrutura interna e externa da Terra, Os agentes formadores e modificadores do relevo), para tanto elaboramos materiais didáticos, utilizando quebra-cabeça, filmes e músicas, que tem por objetivo mediar a informação no processo de ensino-aprendizagem, contribuindo para a transformação do conhecimento. Visto o processo e o avanço técnico cientifico informacional que vivemos, disponibilizar ferramentas que auxiliam a compreensão do mundo e da realidade do local por parte do aluno é essencial para o melhor aproveitamento em aula.PALAVRAS-CHAVE: Ensino-Aprendizagem; Kit Didático; Sequencia Didática